Head injury continues to be a major cause of death and disability throughout the world. A review of the medical literature and our own investigations indicate that hyperbaric oxygen (HBO) has significant potential in the treatment of head injury. Our recently completed prospective clinical trial to assess the effectiveness of HBO in the treatment of severe head injury documented a dramatic improvement in survival. The timing and duration of the HBO therapy as well as potential oxygen toxicity to injured brain are critical issues. The optimal dosing schedule for HBO therapy in brain injury has never been established, neither experimentally or clinically. In addition, our preliminary experimental investigations indicate that the potent antiperoxidation agent, the 21-aminosteroid U74006F, may reduce the toxic effects of oxygen on the injured brain. Our hypothesis is that an optimal HBO treatment schedule in combination with U74006F will act synergistically to reduce intracranial pressure and improve aerobic glucose metabolism while decreasing HBO-induced and brain-injury-produced peroxidation. These treatments in combination will achieve better functional recovery in severe head injury than either treatment alone. Project 1 will determine the optimal dosing for HBO therapy following head trauma in rats. Project 2 will evaluate the efficacy of combining HBO therapy and U74006F in a rat head-injury model. Project 3 will evaluate the physiological effects of HBO therapy on brain-injured humans, specifically cerebral glucose metabolism and intracranial pressure. Valuable information is expected to be gained regarding optimal HBO treatment schedules. The second phase of Project 3 will evaluate combining HBO and U74006F. We anticipate these preliminary studies will lead to a prospective clinical trial to evaluate U74006F and HBO treatment combinations.